Cited by 214Antimicrobial Peptides and ActivitiesCancer Research and TreatmentsHead and Neck Cancer Studies

Nisin ZP, a Bacteriocin and Food Preservative, Inhibits Head and Neck Cancer Tumorigenesis and Prolongs Survival

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Kamarajan, Pachiyappan, Hayami, Takayuki, Matte, Bibiana, Liu, Yang, Danciu, Theodora, Ramamoorthy, Ayyalusamy, Worden, Francis, Kapila, Sunil +1 more·2015·PLOS ONE

Abstract

The use of small antimicrobial peptides or bacteriocins, like nisin, to treat cancer is a new approach that holds great promise. Nisin exemplifies this new approach because it has been used safely in humans for many years as a food preservative, and recent laboratory studies support its anti-tumor potential in head and neck cancer. Previously, we showed that nisin (2.5%, low content) has antitumor potential in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. The current studies explored a naturally occurring variant of nisin (nisin ZP; 95%, high content) for its antitumor effects in vitro and in vivo. Nisin ZP induced the greatest level of apoptosis in HNSCC cells compared to low content nisin. HNSCC cells treated with increasing concentrations of nisin ZP exhibited increasing levels of apoptosis and decreasing levels of cell proliferation, clonogenic capacity, and sphere formation. Nisin ZP induced apoptosis through a calpain-dependent pathway in HNSCC cells but not in human oral keratinocytes. Nisin ZP also induced apoptosis dose-dependently in human umbilical vein endothelial cells (HUVEC) with concomitant decreases in vascular sprout formation in vitro and reduced intratumoral microvessel density in vivo. Nisin ZP reduced tumorigenesis in vivo and long-term treatment with nisin ZP extended survival. In addition, nisin treated mice exhibited normal organ histology with no evidence of inflammation, fibrosis or necrosis. In summary, nisin ZP exhibits greater antitumor effects than low content nisin, and thus has the potential to serve as a novel therapeutic for HNSCC.

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  • Lactococcus lactis produces nisin, a bacteriocin that has been shown to reduce oral tumorigenesis and extend the life span of mice with tumors.

    “Lactococcus lactis, a commensal of the oral microbiota, produces nisin, a bacteriocin that has been shown to reduce oral tumorigenesis and extend the life span of mice with tumors.165, 166”

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Authors
Kamarajan, P., Hayami, T., Matte, B., Liu, Y., Danciu, T., Ramamoorthy, A., Worden, F., Kapila, S., & Kapila, Y.
Affiliations
University of Michigan (US)
Corresponding author
Kapila, Yvonne
Venue
PLOS ONE
Published
2015-07-01
Volume
10
Issue
7
Pages
e0131008
ISSN
1932-6203 (ISSN-L)
OpenAlex
W1871229721
Cited by
214
References
63
Citations by year
2026: 12 · 2025: 22 · 2024: 26 · 2023: 27 · 2022: 31 · 2021: 33 · 2020: 24 · 2019: 9 · 2018: 9 · 2017: 13 · 2016: 5 · 2015: 3
FWCI
8.42
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University of Michigan
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Peking University
  • Ciência sem Fronteiras
  • Division of Graduate Education
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
Keywords
bacteriocins, antimicrobial peptides, head and neck squamous cell carcinoma, anticancer activity, apoptosis, calpain, tumor angiogenesis, microvessel density, carcinogenesis, survival, food preservatives, oral keratinocytes, endothelial cells
MeSH terms
Animals, Carcinoma, Squamous Cell, Dose-Response Relationship, Drug, Flow Cytometry, Head and Neck Neoplasms, Humans, Mice, Nude, Mouth Neoplasms, Neoplasms, Experimental, Neovascularization, Pathologic, Nisin, Blotting, Western, Apoptosis, Cell Line, Tumor, Cell Proliferation, Mice, Microvessels, Carcinogenesis

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